Immunohistochemical expression of molecular markers in an avian model: A potential model for preclinical evaluation of agents for ovarian cancer chemoprevention

Objective. A significant obstacle confronting the evaluation of potential c hemopreventive compounds in ovarian carcinoma is the absence of an animal m odel of spontaneous ovarian carcinogenesis. A potential model of adenocarci noma has been described in the laying hen (Gallus domesticus). The purpose of this study was to evaluate the immunohistochemical expression of availab le antibodies that have been utilized in chemoprevention studies in this po tential model of epithelial carcinoma. Methods. Two hundred 2-year-old hens were sacrificed at Auburn University i n accordance with IUACUC guidelines. Of these hens, 8 animals were thought grossly to have ovarian carcinoma and ascites. The tumors from these 8 hens were fixed in neutral-buffered formalin and processed to paraffin blocks. Hematoxylin and eosin stains were used to document the histologic presence of adenocarcinoma. Immunohistochemical evaluation for expression of antigen was performed using the following antibodies: CA125, CEA, cytokeratin, EGF R, erbB-2, Ki-67, Lewis Y, p27, PCNA, Tag 72, TGF-alpha, Muc 1, and Muc 2. Results. Upon microscopic examination by a pathologist eight specimens were documented as adenocarcinomas. Several antibodies to antigens that are fre quently expressed in human ovarian cancer were cross-reactive in the laying hen. Of these, cytokeratin AE1/AE3, pan cytokeratin, EGFR, Lewis Y, CEA, T ag 72, and erbB-2 stained the chicken carcinomas. EGFR and p185(erbB-2) sta ined diffusely, and cytokeratin AE1/AE3, pan cytokeratin, Lewis Y, CEA, and Tag 72 were focally positive in the tumor. The aforementioned antibodies w hich have been useful as surrogate endpoints in chemoprevention trials and which also stained the chicken carcinomas included PCNA, p27, and TGF-alpha Antibodies that were not cross-reactive include CA 125, Ki-67, Muc 1, and Muc 2. Conclusion. The data presented in this pilot study support the potential ut ility of an avian model of spontaneously arising adenocarcinoma in which to study chemopreventive agents. More importantly, the influence of chemoprev ention protocols on the expression of relevant antigens can be determined u sing available antibodies that are cross-reactive in this model. Thus, chan ges in the phenotypic expression of surrogate endpoint biomarkers as identi fied by cross-reactive antibodies can aid in the development of chemopreven tion trials for human ovarian cancer. (C) 2001 Academic Press.